Chap 20 Objectives 1. Describe the function of the lymphatic system. 2. Explain the structure, distribution, and adaptations of the lymph vessels. 3. Identify the different types of lymphoid cells found in the body. 4. Describe lymphoid tissue. 5. Examine the function of the lymph nodes. 6. List the additional lymphoid organs and explain their function I. Lymphatic Vessels (pp. 772–774; Figs. 20.1–20.2) A. The lymphatic vessels form a one-way system in which lymph flows only toward the heart. B II. 1. The lymphatic transport system starts with the lymph capillaries, found between the tissue cells and blood capillaries, in the loose connective tissue. 2. The lymph capillaries flow into the lymphatic collecting vessels and carry the lymph to the lymphatic trunks. 3. The lymphatic trunks drain fairly large areas of the body and eventually empty the lymph back into the circulatory system via the thoracic duct or the right lymphatic duct. Lymphatic vessels are low-pressure vessels that use the same mechanisms as veins to return the lymph to the circulatory system. Lymphoid Cells and Tissues (p. 775; Fig. 20.3) A. Lymphoid Cells 1. Lymphocytes arise in the red bone marrow and mature into one of two immunocompetent cells: T lymphocytes (T cells) or B lymphocytes (B cells). Instructor’s Resource Guide for Human Anatomy & Physiology 2. Macrophages play an important role in body protection and in activating T lymphocytes. # 3. Dendritic cells, found in lymphoid tissue, also play a role in T lymphocyte activation. 4. Reticular cells produce the stroma, which is the network that supports the other cell types in the lymphoid tissue. B. Lymphoid tissues house and provide a proliferation site for lymphocytes, and furnish an ideal surveillance site for lymphocytes and macrophages. III. Lymph Nodes (pp. 776–777; Fig. 20.4) A. The principle lymphoid organs in the body are the lymph nodes, which act as filters to remove and destroy microorganisms and other debris for the lymph before it is transported back to the bloodstream. B. Each lymph node is surrounded by a dense fibrous capsule with an internal framework, or stroma, of reticular fibers that supports the lymphocytes. C. Lymph enters the convex side of a lymph node through afferent lymphatic vessels, and exists via a fewer number of efferent vessels after passing through several sinuses. IV. Other Lymphoid Organs (pp. 777–782; Figs. 20.5–20.8) A. The spleen is the largest lymphoid organ, located in the left side of the abdominal cavity directly below the diaphragm. 1. The spleen’s main function is to remove old and defective RBCs and platelets as well as foreign matter and debris from the blood. It also provides a site for lymphocyte proliferation and immune surveillance. 2. The spleen is surrounded by a fibrous capsule and contains both lymphocytes found in white pulp, and macrophages found in red pulp. B. Thymus 1. The thymus secretes hormones that cause T lymphocytes to become immunocompetent. 2. The thymus is made up of thymic lobules containing an outer cortex and an inner medulla. C. Tonsils are the simplest lymphoid organs and form a ring of lymphoid tissue around the opening to the pharynx. They appear as swellings of the mucosa that gather and remove many of the pathogens entering the pharynx in food or inhaled air. D. Clusters of lymphoid follicles are found in the wall of the distal portion of the small intestine, Peyer’s patches, and in the appendix. V. Developmental Aspects of the Lymphatic System A. By the fifth week of embryonic development, the beginnings of the lymphatic vessels and the main clusters of lymph nodes are apparent and develop from the budding of lymph sacs from the developing veins. B. The thymus is an endodermal derivative, while the rest of the lymphoid organs derive from the mesoderm. C. Except for the spleen and the tonsils, the lymphoid organs are poorly developed at birth. Chap 21 Objectives Non Specific defenses 1. Explain the roles of the skin and mucous membranes in the innate defense. 2. List and discuss the secretions of the skin and mucous membranes. 3. Describe the different types of phagocytes. 4. Identify the role of natural killer cells. 5. Explain the inflammatory response. 6. Discuss complement, interferon, and fever. Specific Defense System(Immunity) 7. Define antigen and differentiate between self and nonself. Compare a complete and incomplete antigen. 8. Examine the clonal selection and differentiation of B cells. 9. Compare the primary immune response and the secondary immune response. 10. Discuss active and passive immunities, both naturally acquired and artificially acquired. 11. Explain the structure of an antibody. List the five classes of antibodies and their functions. 12. Identify the ways antibodies function. Cell-Mediated Immune Response 13. Discuss clonal selection and differentiation of T cells. Explain how T cells are activated. 14. List the types of T cells and their roles. 15. Describe the different types of tissue grafts involved in organ transplants. Homeostatic Imbalances of Immunity and development 16. Examine immunodeficiencies, autoimmune diseases, and hypersensitivities. 17. Identify the events of embryonic development and the effects of aging on the immune system. I. Innate (Nonspecific) Defenses (pp. 787–796; Figs. 21.1–21.5; Tables 21.1–21.2) A. Surface Barriers: Skin and Mucosae 1. Skin, a highly keratinized epithelial membrane, represents a physical barrier to most microorganisms and their enzymes and toxins. 2. Mucous membranes line all body cavities open to the exterior and function as an additional physical barrier. 3. Secretions of the epithelial tissues include acidic secretions, sebum, hydrochloric acid, saliva, and mucous B. Internal Defenses: Cells and Chemicals 1. Phagocytes confront microorganisms that breach the external barriers. a. Macrophages are the main phagocytes of the body. b. Neutrophils are the first responders and become phagocytic when they encounter infectious material. c. Eosinophils are weakly phagocytic but are important in defending the body against parasitic worms. d. Mast cells have the ability to bind with, ingest, and kill a wide range of bacteria. 2. Natural killer cells are able to lyse and kill cancer cells and virally infected cells before the adaptive immune system has been activated. 3. Inflammation occurs any time the body tissues are injured by physical trauma, intense heat, irritating chemicals, or infection by viruses, fungi, or bacteria. a. The four cardinal signs of acute inflammation are redness, heat, swelling, and pain. b. Chemicals cause dilation of surrounding blood vessels to increase blood flow to the area and increase permeability, which allows fluid containing clotting factors and antibodies to enter the tissues. c. Soon after inflammation the damaged site is invaded by neutrophils and macrophages. 4. Antimicrobial proteins enhance the innate defenses by attacking microorganisms directly or by hindering their ability to reproduce. a. Interferons are small proteins produced by virally infected cells that help protect surrounding healthy cells. b. Complement refers to a group of about 20 plasma proteins that provide a major mechanism for destroying foreign pathogens in the body. 5. II. Fever, or an abnormally high body temperature, is a systemic response to microorganisms. Adaptive (Specific) Defenses (pp. 796–801; Figs. 21.6–21.8) A. Aspects of the Adaptive Immune Response 1. The adaptive defenses recognize and destroy the specific antigen that initiated the response. 2. The immune response is a systemic response; it is not limited to the initial infection site. 3. After an initial exposure the immune response is able to recognize the same antigen and mount a faster and stronger defensive attack. 4. Humoral immunity is provided by antibodies produced by B lymphocytes present in the body’s “humors” or fluids. 5. Cellular immunity is associated with T lymphocytes and has living cells as its protective factor. B. Antigens are substances that can mobilize the immune system and provoke an immune response. 1. Complete antigens are able to stimulate the proliferation of specific lymphocytes and antibodies, and to react with the activated lymphocytes and produced antibodies. 2. Haptens are incomplete antigens that are not capable of stimulating the immune response, but if they interact with proteins of the body they may be recognized as potentially harmful. 3. Antigenic determinates are a specific part of an antigen that are immunogenic and bind to free antibodies or activated lymphocytes. C. Cells of the Adaptive Immune System: An Overview 1. Lymphocytes originate in the bone marrow and when released become immunocompetent in either the thymus (T cells) or the bone marrow (B cells). 2. Antigen-presenting cells engulf antigens and present fragments of these antigens on their surfaces where they can be recognized by T cells. III. Humoral Immune Response (pp. 801–807; Figs. 21.9–21.13; Table 21.3) A. The immunocompetent but naive B lymphocyte is activated when antigens bind to its surface receptors. 1. Clonal selection is the process of the B cell growing and multiplying to form an army of cells that are capable of recognizing the same antigen. 2. Plasma cells are the antibody-secreting cells of the humoral response; most clones develop into plasma cells. 3. The clones that do not become plasma cells develop into memory cells. B. Immunological Memory 1. The primary immune response occurs on first exposure to a particular antigen with a lag time of about 3–6 days. 2. The secondary immune response occurs when someone is reexposed to the same antigen. It is faster, more prolonged, and more effective. C. Active and Passive Humoral Immunity 1. Active immunity occurs when the body mounts an immune response to an antigen. a. Naturally acquired active immunity occurs when a person suffers through the symptoms of an infection. b. Artificially acquired active immunity occurs when a person is given a vaccine. 2. Passive immunity occurs when a person is given preformed antibodies. a. Naturally acquired passive immunity occurs when a mother’s antibodies enter fetal circulation. b. Artificially acquired passive immunity occurs when a person is given preformed antibodies that have been harvested from another person. D. Antibodies or immunoglobulins are proteins secreted by plasma cells in response to an antigen that are capable of binding to that antigen. 1. The basic antibody structure consists of four looping polypeptide chains linked together by disulfide bonds. 2. Antibodies are divided into five classes based on their structure: IgM, IgG, IgA, IgD, and IgE. 3. Embryonic cells contain a few hundred gene segments that are shuffled and combined to form all of the different B cells that are found in the body. 4. Antibody Targets and Functions a. Complement fixation and activation occurs when complement binds to antibodies attached to antigens, and leads to lysis of the cell. b. Neutralization occurs when antibodies block specific sites on viruses or bacterial exotoxins, causing them to lose their toxic effects. c. Agglutination occurs when antibodies cross-link to antigens on cells, causing clumping. d. Precipitation occurs when soluble molecules are cross-linked into large complexes that settle out of solution. 5. Monoclonal antibodies are commercially prepared antibodies specific for a single antigenic determinant. IV. Cell-Mediated Immune Response ( pp. 807–816; Figs. 21.14– 21.18; Table 21.4) A. The stimulus for clonal selection and differentiation of T cells is binding of antigen, although their recognition mechanism is different from B cells. 1. T cells must accomplish a double recognition process: they must recognize both self (an MHC protein of a body cell) and nonself (antigen) at the same time. 2. T Cell Activation a. Step 1: T cell antigen receptors (TCRs) bind to antigen-MHC complex on the surface of a body cell. b. Step 2: A T cell must recognize one or more co-stimulatory signals. c. Once activated, a T cell enlarges and proliferates to form a clone of cells that differentiate and perform functions according to their T cell class. 3. Cytokines include hormonelike glycoproteins released by activated T cells and macrophages. B. Specific T Cell Roles 1. Helper T cells stimulate proliferation of other T cells and B cells that have already become bound to antigen. 2. Cytotoxic T cells, also called killer T cells, are the only T cells that can directly attack and kill other cells displaying antigen to which they have been sensitized. 3. Suppressor T cells release cytokines that suppress the activity of both B cells and other types of T cells. 4. Gamma delta T cells are found in the intestine and are more similar to NK cells than other T cells. 5. Without helper T cells there is no adaptive immune response because the helper T cells direct or help complete the activation of all other immune cells. C. Organ Transplants and Prevention of Rejection 1. Grafts a. Autografts are tissue grafts transplanted from one body site to another in the same person. b. Isografts are grafts donated to a patient by a genetically identical individual such as an identical twin. c. Allografts are grafts transplanted from individuals that are not genetically identical but belong to the same species. d. Xenografts are grafts taken from another animal species. 2. Transplant success depends on the similarity of the tissues because cytotoxic T cells, NK cells, and antibodies work to destroy foreign tissues. V. Homeostatic Balances of Immunity (pp. 818–822) A. Immunodeficiencies are any congenital or acquired conditions that cause immune cells, phagocytes, or complement to behave abnormally. 1. Severe combined immunodeficiency (SCID) is a congenital condition that produces a deficit of B and T cells. 2. Acquired immune deficiency syndrome (AIDS) cripples the immune system by interfering with helper T cells. B. Autoimmune diseases occur when the immune system loses its ability to differentiate between self and nonself and ultimately destroys itself. C. Hypersensitivities, or allergies, are the result of the immune system causing tissue damage as it fights off a perceived threat that would otherwise be harmless. VI. 1. Immediate hypersensitivities begin within seconds after contact and last about half an hour. 2. Subacute hypersensitivities take 1–3 hours to occur and last 10–15 hours. 3. Delayed hypersensitivity reactions take 1–3 days to occur and may take weeks to go away. Developmental Aspects of the Immune System (pp. 823–824) A. Embryologic Development 1. Stem cells of the immune system originate in the liver and spleen during weeks 1–9 of embryonic development; later the bone marrow takes over this role. 2. In late fetal life and shortly after birth the young lymphocytes develop self-tolerance and immunocompetence. B. Later in life the ability and efficiency of our immune system declines. Chap 22 Objectives Functional Anatomy of the Respiratory System 1. List the functions of the nose, nasal cavity, and paranasal sinuses. Describe the function of the pharynx, larynx, and trachea. 2. Explain the function of the lungs and the vascular and neural networks that supply them. 3. Discuss the relationship of the pleurae to the lungs and thoracic wall, and their functional importance. Mechanics of Breathing (Verntilation) 5. Define intrapulmonary and intrapleural pressure. 6. Describe pulmonary ventilation and the relationships between pressure and volume changes as they apply to the lungs. 7. Identify the events of quiet and forced inspiration, and passive and forced expiration. 8. Discuss the effects of airway resistance, alveolar surface tension, and lung compliance on pulmonary ventilation. 9. List and define the respiratory volumes and capacities. TV, VC, ERV, IRV, FEV1 10. Distinguish between obstructive and restrictive respiratory disorders, and describe the role of pulmonary function tests in distinguishing between them. 11. Name the nonrespiratory air movements. Basic Properties of Gases 12. Define Dalton’s law of partial pressures, and relate it to atmospheric gases. 13. Explain Henry’s law, and describe its importance to gas exchange in the lungs. Composition of Alveolar Gas 14. Compare the composition of alveolar gases to atmospheric gases. Gas Exchanges Between the Blood, Lungs, and Tissues 15. Define external respiration and pulmonary gas exchange, and describe the factors that affect exchange. Transport of Respiratory Gases by Blood 16. Describe how oxygen and carbon dioxide are carried in the blood, and explain the role of hemoglobin. Control of Respiration 17. List the neural structures that control respiration, and the factors that affect rate and depth of respiration. Respiratory Adjustments 18. Explain the adjustments to respiration that occur in response to exercise and increased altitude. Homeostatic Imbalances of the Respiratory System 19. Identify the characteristics of chronic obstructive pulmonary disorders, asthma, tuberculosis, and lung cancer. Developmental Aspects of the Respiratory System 20. Describe the events of development and growth of the respiratory system. 21. List the changes that occur in the respiratory system with age. Chapter 22: The Respiratory System I. Functional Anatomy of the Respiratory System (pp. 829–844; Figs. 22.1–22.11; Table 22.1) A. The Nose and Paranasal Sinuses (pp. 829–833; Figs. 22.1–22.3) 1. The nose provides an airway for respiration; moistens, warms, filters, and cleans incoming air; provides a resonance chamber for speech; and houses olfactory receptors. 2. The nose is divided into the external nose, which is formed by hyaline cartilage and bones of the skull, and the nasal cavity, which is entirely within the skull. 3. The nasal cavity consists of two types of epithelium: olfactory mucosa and respiratory mucosa. 4. The nasal cavity is surrounded by paranasal sinuses within the frontal, maxillary, sphenoid, and ethmoid bones that serve to lighten the skull, warm and moisten air, and produce mucus. B. The Pharynx (p. 833) 1. The pharynx connects the nasal cavity and mouth superiorly to the larynx and esophagus inferiorly. a. The nasopharynx serves as only an air passageway, and contains the pharyngeal tonsil, which traps and destroys airborne pathogens. b. The oropharynx is an air and food passageway that extends inferiorly from the level of the soft palate to the epiglottis. c. The laryngopharynx is an air and food passageway that lies directly posterior to the epiglottis, extends to the larynx, and is continuous inferiorly with the esophagus. C. The Larynx (pp. 833–836; Figs. 22.4–22.5) 1. The larynx attaches superiorly to the hyoid bone, opening into the laryngopharynx, and attaches inferiorly to the trachea. 2. The larynx provides an open airway, routes food and air into the proper passageways, and produces sound through the vocal cords. 3. The larynx consists of hyaline cartilages: thyroid, cricoid, paired arytenoid, corniculate, and cuneiform; and the epiglottis, which is elastic cartilage. 4. Vocal ligaments form the core of mucosal folds, the true vocal cords, which vibrate as air passes over them to produce sound. 5. The vocal folds and the medial space between them are called the glottis. 6. Voice production involves the intermittent release of expired air and the opening and closing of the glottis. 7. Valsalva’s maneuver is a behavior in which the glottis closes to prevent exhalation and the abdominal muscles contract, causing intra-abdominal pressure to rise. D. The trachea, or windpipe, descends from the larynx through the neck into the mediastinum, where it terminates at the primary bronchi (pp. 837–838; Fig. 22.6). E. The Bronchi and Subdivisions: The Bronchial Tree (pp. 838–840; Figs. 22.7–22.8) # Instructor’s Resource Guide for Human Anatomy & Physiology 1. The conducting zone consists of right and left primary bronchi that enter each lung and diverge into secondary bronchi that serve each lobe of the lungs. 2. Secondary bronchi branch into several orders of tertiary bronchi, which ultimately branch into bronchioles. 3. As the conducting airways become smaller, the supportive cartilage changes in character until it is no longer present in the bronchioles. 4. The respiratory zone begins as the terminal bronchioles feed into respiratory bronchioles that terminate in alveolar ducts within clusters of alveolar sacs, which consist of alveoli. a. The respiratory membrane consists of a single layer of squamous epithelium, type-I cells, surrounded by a basal lamina. b. Interspersed among the type-I cells are cuboidal type-II cells that secrete surfactant. c. Alveoli are surrounded by elastic fibers, contain open alveolar pores, and have alveolar macrophages. F. The Lungs and Pleurae (pp. 840–844; Figs. 22.9–22.11) 1. The lungs occupy all of the thoracic cavity except for the mediastinum; each lung is suspended within its own pleural cavity and connected to the mediastinum by vascular and bronchial attachments called the lung root. 2. Each lobe contains a number of bronchopulmonary segments, each served by its own artery, vein, and tertiary bronchus. 3. Lung tissue consists largely of air spaces, with the balance of lung tissue, its stroma, comprised mostly of elastic connective tissue. 4. There are two circulations that serve the lungs: the pulmonary network carries systemic blood to the lungs for oxygenation, and the bronchial arteries provide systemic blood to the lung tissue. 5. The lungs are innervated by parasympathetic and sympathetic motor fibers that constrict or dilate the airways, as well as visceral sensory fibers. 6. The pleurae form a thin, double-layered serosa. a. The parietal pleura covers the thoracic wall, superior face of the diaphragm, and continues around the heart between the lungs. b. The visceral pleura covers the external lung surface, following its contours and fissures. II. Mechanics of Breathing (pp. 844–852; Figs. 22.12–22.16; Tables 22.2–22.3) A. Pressure Relationships in the Thoracic Cavity (pp. 844–845; Fig. 22.12) 1. Intrapulmonary pressure is the pressure in the alveoli, which rises and falls during respiration, but always eventually equalizes with atmospheric pressure. 2. Intrapleural pressure is the pressure in the pleural cavity. It also rises and falls during respiration, but is always about 4 mm Hg less than intrapulmonary pressure. B. Pulmonary Ventilation: Inspiration and Expiration (pp. 845–847; Figs. 22.13–22.14) 1. Pulmonary ventilation is a mechanical process causing gas flow into and out of the lungs according to volume changes in the thoracic cavity. a. Boyle’s law states that at a constant temperature, the pressure of a gas varies inversely with its volume. 2. During quiet inspiration, the diaphragm and intercostals contract, resulting in an increase in thoracic volume, which causes intrapulmonary pressure to drop below atmospheric pressure, and air flows into the lungs. 3. During forced inspiration, accessory muscles of the neck and thorax contract, increasing thoracic volume beyond the increase in volume during quiet inspiration. 4. Quiet expiration is a passive process that relies mostly on elastic recoil of the lungs as the thoracic muscles relax. 5. Forced expiration is an active process relying on contraction of abdominal muscles to increase intra-abdominal pressure and depress the ribcage. C. Physical Factors Influencing Pulmonary Ventilation (pp. 847–849; Fig. 22.15) 1. Airway resistance is the friction encountered by air in the airways; gas flow is reduced as airway resistance increases. 2. Alveolar surface tension due to water in the alveoli acts to draw the walls of the alveoli together, presenting a force that must be overcome in order to expand the lungs. 3. Lung compliance is determined by distensibility of lung tissue and the surrounding thoracic cage, and alveolar surface tension. D. Respiratory Volumes and Pulmonary Function Tests (pp. 849–852; Fig. 22.16; Tables 22.2–22.3) 1. Respiratory volumes and specific combinations of volumes, called respiratory capacities, are used to gain information about a person’s respiratory status. a. Tidal volume is the amount of air that moves in and out of the lungs with each breath during quiet breathing. b. The inspiratory reserve volume is the amount of air that can be forcibly inspired beyond the tidal volume. c. The expiratory reserve volume is the amount of air that can be evacuated from the lungs after tidal expiration. d. Residual volume is the amount of air that remains in the lungs after maximal forced expiration. e. Inspiratory capacity is the sum of tidal volume and inspiratory reserve volume, and represents the total amount of air that can be inspired after a tidal expiration. f. Functional residual capacity is the combined residual volume and expiratory reserve volume, and represents the amount of air that remains in the lungs after a tidal expiration. g. Vital capacity is the sum of tidal volume, inspiratory reserve and expiratory reserve volumes, and is the total amount of exchangeable air. h. Total lung capacity is the sum of all lung volumes. 2. The anatomical dead space is the volume of the conducting zone conduits, which is a volume that never contributes to gas exchange in the lungs. 3. Pulmonary function tests evaluate losses in respiratory function using a spirometer to distinguish between obstructive and restrictive pulmonary disorders. 4. Nonrespiratory air movements cause movement of air into or out of the lungs, but are not related to breathing (coughing, sneezing, crying, laughing, hiccups, and yawning). III. Basic Properties of Gases (pp. 852–853; Table 22.4) A. Dalton’s law of partial pressure states that the total pressure exerted by a mixture of gases is the sum of the pressures exerted independently by each gas in the mixture (p. 852). B. Henry’s law states that when a mixture of gases is in contact with a liquid, each gas will dissolve in the liquid in proportion to its partial pressure (pp. 852–853). IV. Composition of Alveolar Gas (p. 853; Table 22.4) A. The relative proportions of gases in the alveoli reflect gas exchange occurring in the lungs, humidification of air by conducting passages, and mixing of alveolar gas that occurs with each breath. V. Gas Exchanges Between the Blood, Lungs, and Tissues (pp. 853– 856; Figs. 22.17–22.20) A. External Respiration: Pulmonary Gas Exchange (pp. 854–856; Figs. 22.17–22.19) 1. External respiration involves O2 uptake and CO2 unloading from hemoglobin in red blood cells. a. A steep partial pressure gradient exists between blood in the pulmonary arteries and alveoli, and O2 diffuses rapidly from the alveoli into the blood, but carbon dioxide moves in the opposite direction along a partial pressure gradient that is much less steep. b. The difference in the degree of the partial pressure gradients of oxygen and carbon dioxide reflects the fact that carbon dioxide is much more soluble than oxygen in the blood. c. Ventilation-perfusion coupling ensures a close match between the amount of gas reaching the alveoli and the blood flow in the pulmonary capillaries. d. The respiratory membrane is normally very thin, and presents a huge surface area for efficient gas exchange. B. Internal Respiration: Capillary Gas Exchange in the Body Tissues (p. 856) 1. The diffusion gradients for oxygen and carbon dioxide are reversed from those for external respiration and pulmonary gas exchange. 2. The partial pressure of oxygen in the tissues is always lower than the blood, so oxygen diffuses readily into the tissues, while a similar but less dramatic gradient exists in the reverse direction for carbon dioxide. VI. Transport of Respiratory Gases by Blood (pp. 856–861; Figs. 22.20–22.23) A. Oxygen Transport (pp. 856–859; Figs. 22.20–22.22) 1. Since molecular oxygen is poorly soluble in the blood, only 1.5% is dissolved in plasma, while the remaining 98.5% must be carried on hemoglobin. a. Up to four oxygen molecules can be reversibly bound to a molecule of hemoglobin—one oxygen on each iron. b. The affinity of hemoglobin for oxygen changes with each successive oxygen that is bound or released, making oxygen loading and unloading very efficient. 2. At higher plasma partial pressures of oxygen, hemoglobin unloads little oxygen, but if plasma partial pressure falls dramatically, i.e. during vigorous exercise, much more oxygen can be unloaded to the tissues. 3. Temperature, blood pH, PCO2, and the amount of BPG in the blood all influence hemoglobin saturation at a given partial pressure. 4. Nitric oxide (NO), secreted by lung and vascular endothelial cells, is carried on hemoglobin to the tissues where it causes vasodilation and enhances oxygen transfer to the tissues. B. Carbon Dioxide Transport (pp. 859–861; Figs. 22.22–22.23) 1. Carbon dioxide is transported in the blood in three ways: 7–10% is dissolved in plasma, 20% is carried on hemoglobin bound to globins, and 70% exists as bicarbonate, an important buffer of blood pH. 2. The Haldane effect encourages CO2 exchange in the lungs and tissues: when plasma partial pressure of oxygen and oxygen saturation of hemoglobin decrease, more CO 2 can be carried in the blood. 3. The carbonic acid–bicarbonate buffer system of the blood is formed when CO 2 combines with water and dissociates, producing carbonic acid and bicarbonate ions that can release or absorb hydrogen ions. VII. Control of Respiration (pp. 861–867; Figs. 22.24–22.27) A. Neural Mechanisms and Generation of Breathing Rhythm (pp. 861–863; Figs. 22.24–22.25) 1. The medulla oblongata contains the dorsal respiratory group, or inspiratory center, with neurons that act as the pacesetting respiratory group, and the ventral respiratory group, which functions mostly during forced breathing. 2. The pontine respiratory group within the pons modifies the breathing rhythm and prevents overinflation of the lungs through an inhibitory action on the medullary respiration centers. 3. It is likely that reciprocal inhibition on the part of the different respiratory centers is responsible for the rhythm of breathing. B. Factors Influencing Breathing Rate and Depth (pp. 863–867; Figs. 22.25–22.27) 1. Pulmonary irritant reflexes respond to inhaled irritants by causing reflex constriction of the irritated passageways if the trachea or nasal cavity is irritated. 2. The inflation, or Hering-Breuer, reflex is activated by stretch receptors in the visceral pleurae and conducting airways, resulting in inhibition of inspiration. 3. Influence of Higher Brain Centers a. The limbic system, strong emotions, and pain activate the hypothalamus, which modifies respiratory rate and depth. b. The cerebral cortex can exert voluntary control over respiration by bypassing the medullary centers and directly stimulating the respiratory muscles. 4. Chemical Factors a. Plasma and cerebrospinal fluid levels of P CO2 are the strongest stimuli influencing respiration; elevated PCO2, or hypercapnia, causes an increase in rate and depth of breathing. b. Blood PO2 affects breathing indirectly by influencing chemoreceptor sensitivity to changes in PCO2. c. Peripheral chemoreceptors monitor plasma P O2 and stimulate an increase in ventilation when PO2 drops below 60 mm Hg. d. As arterial pH declines, the respiratory system attempts to compensate by causing an increase in rate and depth of breathing. VIII. Respiratory Adjustments (pp. 868–869) A. Adjustments During Exercise (p. 868) 1. During vigorous exercise, deeper and more vigorous respirations, called hyperpnea, ensure that tissue demands for oxygen are met. 2. Three neural factors contribute to the change in respiration: psychic stimuli, cortical stimulation of skeletal muscles and respiratory centers, and excitatory impulses to the respiratory areas from active muscles, tendons, and joints. B. Adjustments at High Altitude (pp. 868–869) 1. Acute mountain sickness (AMS) may result from a rapid transition from sea level to altitudes above 8000 feet. 2. A long-term change from sea level to high altitudes results in acclimatization of the body, including an increase in ventilation rate, lower than normal hemoglobin saturation, and increased production of erythropoietin. IX. Homeostatic Imbalances of the Respiratory System (pp. 869– 871; Fig. 22.28) A. Chronic obstructive pulmonary diseases (COPD) are seen in patients that have a history of smoking, and result in progressive dyspnea, coughing and frequent pulmonary infections, and respiratory failure. 1. Obstructive emphysema is characterized by permanently enlarged alveoli and deterioration of alveolar walls. 2. Chronic bronchitis results in excessive mucus production, as well as inflammation and fibrosis of the lower respiratory mucosa. B. Asthma is characterized by coughing, dyspnea, wheezing, and chest tightness, brought on by active inflammation of the airways (p. 870). C. Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis and spread by coughing and inhalation (p. 870). D. Lung Cancer (pp. 870–871) 1. In both sexes, lung cancer is the most common type of malignancy, and is strongly correlated with smoking. 2. Squamous cell carcinoma arises in the epithelium of the bronchi, and tends to form masses that hollow out and bleed. 3. Adenocarcinoma originates in peripheral lung areas as nodules that develop from bronchial glands and alveolar cells. 4. Small cell carcinoma contains lymphocyte-like cells that form clusters within the mediastinum and rapidly metastasize. X. Developmental Aspects of the Respiratory System (pp. 871–873; Fig. 22.29) A. By the fourth week of development, the olfactory placodes are present and give rise to olfactory pits that form the nasal cavities. B. The nasal cavity extends posteriorly to join the foregut, which gives rise to an outpocketing that becomes the pharyngeal mucosa. C. By the eighth week of development, mesoderm forms the walls of the respiratory passageways and stroma of the lungs. D. As a fetus, the lungs are filled with fluid, and vascular shunts are present that divert blood away from the lungs; at birth, the fluid drains away, and rising plasma P CO2 stimulates respiratory centers. E. Respiratory rate is highest in newborns, and gradually declines to adulthood; in old age, respiratory rate increases again. F. As we age, the thoracic wall becomes more rigid, the lungs lose elasticity, and the amount of oxygen we can use during aerobic respiration decreases. G. The number of mucus glands and blood flow in the nasal mucosa decline with age, as does ciliary action of the mucosa, and macrophage activity.